Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells in Chronic versus Acute Infection

David Wolski 1, 2 Peter Foote 1 Diana Chen 1 Lia Lewis-Ximenez 3 Catherine Fauvelle 2 Jasneet Aneja 1 Andreas Walker 4 Pierre Tonnerre 1 Almudena Torres-Cornejo 1 Daniel Kvistad 1 Sabrina Imam 5 Michael Waring 6, 7 Damien Tully 6 Todd Allen 6 Raymond Chung 1 Jörg Timm 4 W. Nicholas Haining 5 Arthur Kim 8 Thomas Baumert 2, 9, * Georg Lauer 1, *
* Corresponding author
1 Liver Center - Department of Medicine - Gastrointestinal Division [Boston, MA, USA]
2 IVH - Institut de Recherche sur les Maladies Virales et Hépatiques
3 Laboratory of Viral Hepatitis [Rio de Janeiro, Brazil]
4 Institute for Virology [Düsseldorf, Germany]
5 Department of Pediatric Oncology [Boston, MA, USA]
6 Ragon Institute of MGH, MIT and Harvard
7 HHMI - Howard Hughes Medical Institute [Chevy Chase]
8 Department of Infectious Disease [Boston]
9 Pôle hépato-digestif [Strasbourg]
Abstract : Distinct molecular pathways govern the differentiation of CD8+ effector T cells into memory or exhausted T cells during acute and chronic viral infection, but these are not well studied in humans. Here, we employed an integrative systems immunology approach to identify transcriptional commonalities and differences between virus-specific CD8+ T cells from patients with persistent and spontaneously resolving hepatitis C virus (HCV) infection during the acute phase. We observed dysregulation of metabolic processes during early persistent infection that was linked to changes in expression of genes related to nucleosomal regulation of transcription, T cell differentiation, and the inflammatory response and correlated with subject age, sex, and the presence of HCV-specific CD4+ T cell populations. These early changes in HCV-specific CD8+ T cell transcription preceded the overt establishment of T cell exhaustion, making this signature a prime target in the search for the regulatory origins of T cell dysfunction in chronic viral infection. Copyright © 2017 Elsevier Inc. All rights reserved.
Keywords : CD8 T cells CD4 T cell help T cell dysfunction adaptive immunity hepatitis C virus metabolism network analysis nucleosome transcriptional regulation viral escape
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David Wolski, Peter Foote, Diana Chen, Lia Lewis-Ximenez, Catherine Fauvelle, et al.. Early Transcriptional Divergence Marks Virus-Specific Primary Human CD8+ T Cells in Chronic versus Acute Infection. Immunity, Elsevier, 2017, 47 (4), pp.648-663.e8. ⟨10.1016/j.immuni.2017.09.006⟩. ⟨inserm-02315536⟩

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